Gonadal (Testicular and Ovarian Tumors)

Gonadal (Testicular and Ovarian Tumors) Gonadal (Testicular and Ovarian Tumors) Authors: Ayda G. Nambayan, DSN, RN, St. Jude Children’s Research Hospital Erin Gafford, Pediatric Oncology Education Student, St. Jude Children’s Research Hospital; Nursing Student, School of Nursing, Union University Content Reviewed by: Guillermo L. Chantada, MD, Hospital JP Garrahan, Buenos Aires, Argentina Cure4Kids Release Date: 1 September 2006 At 4 weeks gestation, germ cells begin to develop in the yolk sac in an undifferentiated state. These primordial germ cells migrate to the gonadal ridge by the 6th week of gestation, and descend into the pelvis or scrotal sac. This migratory route explains the midline location of most extra-gonadal germ cell tumors (intracranial, mediastinal, retroperitoneal or sacrococcygeal). <a href="#5_0">(A -1 ) Germ cell neoplasms </a>arise either from the primordial germ cells (gonadal) or indirectly through embryonic or extra-embryonic differentiation (extra-gonadal). The stromal tumors arise from the primitive sex cords of either the ovary or the testicles, and the rare epithelial tumors arise from the coelomic epithelium that have undergone neoplastic transformations. Though the morphology of each type of germ cell tumor is similar in all locations (whether gonadal or extragonadal), the morphologic type and biological characteristics vary depending on the site of origin and age of the patient. There are three <a href="#7_0">(A – 2) biologically distinct subsets </a>of germ cell tumors: ---tumors of the adolescent testis and ovary extragonadal germ cell tumors of older children tumors of infants and young children Testicular Germ Cell Tumors: Approximately 7% of all germ cell tumors are testicular and 75% of all <a href="#7_1">(A – 3) testicular tumors </a>have a germ cell origin. Though 90% are localized, metastatic disease can occur in the lymph nodes of the chest and retroperitoneum. Risk factors include undescended testes; and patients who have orchidopexy should be examined for occurrence of testicular tumors. Most commonly, patients present with a painless, irregular scrotal mass, often associated with hydroceles or inguinal hernias. Most testicular tumors are noted during routine examination or observed by the child’s caretaker. These tumors are irregular, non-tender scrotal masses. In some cases, a hydrocele and inguinal hernia may also be present. <ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 1 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) Diagnostic Workup:  Complete history of illness to evaluate for associated symptoms such as constipation, vomiting, genitourinary symptoms.  Physical exam to assess for masses, inguinal hernias, hydoceles  Ultrasound to determine cystic versus solid characteristics and detect calcifications; localize the scrotal mass, and differentiate between simple and reactive hydrocele.  Assessment of serum tumor markers AFP and β-hCG, which are often elevated, since most testicular tumors are of the yolk pathology. These serum markers serve as the basis for staging and monitoring treatment efficacy.  Metastatic evaluation including CT scan, and ultrasound of the pelvis, abdomen and pelvis; chest X-ray, and bone scintigraphy. Staging for Testicular Cancers: A <a href="#8_0">(A – 4) staging system </a>developed by the Pediatric Oncology Group and the Children’s Cancer Group that accounts for tumor markers and the trans-scrotal surgery of the tumors. Ovarian Tumors: Ovarian tumors represent approximately 1% of childhood malignancies and are often seen during the first and second decades of life. Two -thirds of all ovarian tumors are of germ cell origin, most commonly benign teratomas. <a href="#9_0">(A – 5) Malignant ovarian tumors</a><a href="#9_0"> </a>include dysgerminoma, yolk sac (endodermal sinus), embryonal carcinoma, mixed germ cell tumor, and immature teratoma. Patients often complain of abdominal distention, varying degrees of acute and chronic abdominal pain, and a palpable abdominal mass. Other symptoms include enuresis, constipation, amenorrhea, precocious puberty, and vaginal bleeding. Diagnostic Workup:  Complete history of illness to evaluate for associated symptoms such as vaginal bleeding, amenorrhea, and a review of the menstrual history, if applicable, should be done.  Physical exam to assess for <a href="#9_1">(A – 6) abdominal mass </a>and presence of secondary sex characteristics (presence of precocious puberty)  Ultrasound to evaluate pelvic masses, localize adnexal masses, differentiate between solid and cystic masses, and to detect calcifications.  Abdominal and pelvic CT scans to define the site of origin, tumor extent, presence of calcifications, fat and metastatic disease  Assess serum tumor markers AFP, β-hCG, carcinoembryonic antigen, and CA-125. These serum markers serve as basis for staging and monitoring treatment efficacy.  Metastatic evaluation by CT scan, ultrasound of the pelvis, abdomen and pelvis, chest X- ray, CT and bone scintigraphy. CNS imaging may be necessary in patients with disseminated disease. <ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 2 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) Staging for Ovarian Cancers: A staging system currently used for ovarian cancers in the adult population developed by the <a href="#10_0">(A-7) International Federation of Gynecology and Obstetrics (FIGO) </a>serves as a basis for a simpler system being used by the <a href="#11_0">(A-8) Pediatric Oncology Group/Children’s Cancer Group </a>(POG\CCG) in their cooperative studies. Treatment: Treatment for germ cell tumors should be multimodal and individualized. Surgical resection is the treatment of choice in treating benign germ cell tumors and is also important in treating malignant tumors if removal does not sacrifice vital structures. In cases of tumors that are unresectable, chemotherapy can sometimes be used to debulk some tumors so that they can be resected. Young patients with completely excised testicular yolk sac tumors whose AFP values return to normal after surgery, may be managed without adjuvant therapy and monitored closely with serial AFP levels for early detection of relapse. Standard agents currently used in the Germ Cell Tumor Protocols include cisplatin (platinol), etoposide (VP – 16), and bleomycin (PEB). Newer agents include ifosfamide (Ifex), carboplatin, and topotecan. Even though dysgerminomas are exquisitely radiosensitive, this modality has been recently replaced by chemotherapy in most cases. The introduction of effective chemotherapy has greatly improved the prognosis of germ cell tumors. Relapsing patients with chemosensitive disease can be rescued with higher dose chemotherapy. Future Directions: The challenges for germ cell tumors include further understanding these diverse tumors through risk groupings, identification of molecular and genetic alterations associated with these tumors, and the development of novel therapies with lower toxicity and fewer late effects than current drugs. <ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 3 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) Helpful Web links: Lucile Packard Children’s Hospital at Stanford, Palo Alto, CA <a href="/goto?url=http://www.lpch.org/diseaseHealthInfo/healthLibrary/oncology/gct.html" target="_blank">http://www.lpch.org/diseaseHealthInfo/healthLibrary/oncology/gct.html </a>St. Jude Children's Research Hospital <a href="/goto?url=http://www.stjude.org/disease-summaries/0,2557,449_2167_7407,00.html" target="_blank">http://www.stjude.org/disease-summaries/0,2557,449_2167_7407,00.html </a>eMedicine.com – Teratomas and Other Germ Cell Tumors <a href="/goto?url=http://www.emedicine.com/ped/topic3023.htm" target="_blank">http://www.emedicine.com/ped/topic3023.htm </a>eMedicine.com - Germ Cell Tumors <a href="/goto?url=http://www.emedicine.com/med/topic863.htm" target="_blank">http://www.emedicine.com/med/topic863.htm </a>The National Cancer Institute This website contains comprehensive information on extracranial germ cell tumors. <a href="/goto?url=http://jncicancerspectrum.oxfordjournals.org/cgi/pdq/jncipdq;CDR0000062854" target="_blank">http://jncicancerspectrum.oxfordjournals.org/cgi/pdq/jncipdq;CDR0000062854 </a>Related <a href="/goto?url=http://www.cure4kids.org/" target="_blank">www.Cure4kids.org </a>Seminars Seminar #658 <a href="/goto?url=https://www.cure4kids.org/seminar/658" target="_blank">Ovarian Masses in Pediatric Age Groups </a>Himesh Gupta, MD, Stephen Shochat, MD, Joseph D. Khoury, MD and Fredric Hoffer, MD <a href="/goto?url=https://www.cure4kids.org/seminar/658" target="_blank">https://www.cure4kids.org/seminar/658 </a><ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 4 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) Embryonic Gonads Mesenchymal Tissue APPENDIX: <ul style="display: flex;"><li style="flex:1">A – 1 </li><li style="flex:1">Histogenesis of the Gonadal Tumors </li></ul><ul style="display: flex;"><li style="flex:1">Primordial germ cell </li><li style="flex:1">Celomic epithelium </li></ul>:<ul style="display: flex;"><li style="flex:1">Dysgerminoma </li><li style="flex:1">Sex-cord stromal </li></ul>tumors Epithelial tumors Embryonal differentiation Embryonal carcinoma Extra-embryonic tumors Endodermal sinus tumor <ul style="display: flex;"><li style="flex:1">Choriocarcinoma </li><li style="flex:1">Embryonic tumors </li></ul>Teratoma Polyembryoma Distribution and Characteristics of Germ Cell Tumors: Germ Cell Tumor <ul style="display: flex;"><li style="flex:1">Median Age </li><li style="flex:1">Pathology </li><li style="flex:1">Clinical </li></ul>Presentation Gonadal <ul style="display: flex;"><li style="flex:1">Pre-adolescents & Dysgerminomas </li><li style="flex:1">Palpable abdominal </li></ul><ul style="display: flex;"><li style="flex:1">mass </li><li style="flex:1">Ovarian </li><li style="flex:1">adolescents </li><li style="flex:1">Yolk sac tumors </li></ul><ul style="display: flex;"><li style="flex:1">(10 – 14 years) </li><li style="flex:1">Immature teratoma </li></ul>Malignant mixed germ cell tumors Embryonal carcinomas Abdominal distention Varying degree of acute or chronic abdominal pain. - depending on patient age, histology and the presence of ovarian torsion Infants Adolescents Endodermal sinus tumor (yolk sac) <ul style="display: flex;"><li style="flex:1">teratomas </li><li style="flex:1">Testicular </li></ul>Irregular, non tender scrotal mass <ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 5 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) Germ Cell Tumor <ul style="display: flex;"><li style="flex:1">Median Age </li><li style="flex:1">Pathology </li><li style="flex:1">Clinical </li></ul>Presentation Extragonadal <ul style="display: flex;"><li style="flex:1">Infancy </li><li style="flex:1">Endodermal sinus tumor (Yolk sac) </li></ul>Embryonal Variable – depending upon <ul style="display: flex;"><li style="flex:1">location and histology </li><li style="flex:1">Sacrococcygeal </li></ul>Benign Teratoma Immature Malignant <ul style="display: flex;"><li style="flex:1">Children </li><li style="flex:1">Teratoma </li><li style="flex:1">Coughing </li></ul>Mediastinal anterior superior <ul style="display: flex;"><li style="flex:1">Adolescents </li><li style="flex:1">Embryonal carcinoma </li></ul>Endodermal sinus tumor (yolk sac) Choriocarcinoma Wheezing Dyspnea Chest pain especially in large <ul style="display: flex;"><li style="flex:1">tumors </li><li style="flex:1">posterior </li></ul>Under 2 years Children <ul style="display: flex;"><li style="flex:1">Benign or malignant </li><li style="flex:1">Abdominal pain </li></ul>Constipation Urinary difficulties Abdominal Retroperitoneum Stomach Omentum Liver <ul style="display: flex;"><li style="flex:1">Germinomas </li><li style="flex:1">Headaches </li></ul>Intracranial Pineal Suprasellar Infrasellar Non-germinomas Mixed with yolk sac Choriocarcinoma Teratocarcinoma Visual disturbances Incoordination Diabetes Insipidus Hypopituitaris, Anorexia Precocious puberty <ul style="display: flex;"><li style="flex:1">Infants </li><li style="flex:1">Usually benign </li><li style="flex:1">Variable, depending upon </li></ul><ul style="display: flex;"><li style="flex:1">location </li><li style="flex:1">Head and Neck </li></ul>Oral cavity Pharynx Orbit Neck Upper jaw <ul style="display: flex;"><li style="flex:1">Under 3 years </li><li style="flex:1">Usually malignant </li><li style="flex:1">Blood-tinged vaginal </li></ul><ul style="display: flex;"><li style="flex:1">discharge </li><li style="flex:1">Vaginal </li></ul>Castleberry, R. et.al. Germ Cell Tumors in Principles and Practice of Pediatric Oncology, Pizzo, P. and Poplack, D. (Eds). Lippincott-Raven Press Go Back <ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 6 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) <ul style="display: flex;"><li style="flex:1">A – 2 </li><li style="flex:1">Biological Subsets and corresponding molecular\genetic alterations </li></ul><ul style="display: flex;"><li style="flex:1">Biological Subsets </li><li style="flex:1">Molecular and genetic alterations </li></ul>Testis: C-kit expression <ul style="display: flex;"><li style="flex:1">Tumors of the adolescent testis and ovary </li><li style="flex:1">Multiple copies of i(12p) </li></ul>LOH 12q13, 12q22, 11p13, 11p15 K-ras and N-ras mutation Ovary: C-kit expression MGF expression Aneuploidy Extra-gonadal germ cell tumors of older children Tumors of infants and young children Increased copies if the x chromosome Diploidy and tetraploidy Presence of i(12p) in some pineal tumors Biologic similarity between gonadal and extragonadal tumors Diploid with normal karyotypes Chromosomal abnormalities in 1, 3 and 6 Deletion of 1p36 Go Back <ul style="display: flex;"><li style="flex:1">A – 3 </li><li style="flex:1">Clinical Features of Pediatric Testicular Tumors </li></ul><ul style="display: flex;"><li style="flex:1">Tumor Type </li><li style="flex:1">Median Age </li><li style="flex:1">Clinical Features </li></ul><ul style="display: flex;"><li style="flex:1">Endodermal Sinus Tumor </li><li style="flex:1">2 years </li><li style="flex:1">Most common malignant tumor of the </li></ul>testes  AFP, tumors are histologically pure 85% are in stage I chemotherapy used in higher stage and recurrent disease <ul style="display: flex;"><li style="flex:1">Teratoma </li><li style="flex:1">3 years </li><li style="flex:1">Histologically poorly differentiated – </li></ul>amenable to surgery alone <ul style="display: flex;"><li style="flex:1">Embryonal Carcinoma </li><li style="flex:1">Late teens </li><li style="flex:1">Uncommon in young children </li></ul> AFP + hCG managed with lymphadenectomy + chemotherapy + radiation therapy (based on stage) 80% Stage I with 75% survival rate with surgery alone advanced disease requires multimodal therapy Associated with sexual maldevelopment syndrome Treatment of choice -Bilateral resection of the gonads Teratocarcinoma Gonadoblastoma Late teens 5 to 10 years <ul style="display: flex;"><li style="flex:1">---- </li><li style="flex:1">Others (Seminoma, mixed germ </li></ul>cell tumor, choriocarcinoma) rare in children Castleberry, R. et.al. Germ Cell Tumors in Principles and Practice of Pediatric Oncology, Pizzo, P. and Poplack, D. (Eds). Lippincott-Raven Press Go Back <ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 7 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) <ul style="display: flex;"><li style="flex:1">Testicular Cancer Staging System </li><li style="flex:1">A – 4 </li></ul>Pediatric Oncology Group/Children’s Cancer Group (POG/CCG) <ul style="display: flex;"><li style="flex:1">Stage </li><li style="flex:1">Extent of Disease </li></ul><ul style="display: flex;"><li style="flex:1">Stage I </li><li style="flex:1">Limited to the testes </li></ul>Complete resection by high inguinal orchiectomy or transscrotal orchiectomy without spill No clinical, radiographic, or histologic evidence of disease beyond the testes Tumor markers normal after appropriate post-surgical half-life decline; patients with normal or unknown markers at diagnosis must have a negative ipsilateral retroperitoneal node dissection to confirm Stage I Transscrotal orchiectomy with gross spill of the tumor Microscopic disease in scrotum or high in spermatic cord (< 5cm from proximal end) Stage II Retroperitoneal lymph node involvement (< 2cm) Increased tumor markers after appropriate half life Stage III Retroperitoneal lymph node involvement (>2cm) No visceral or extra-abdominal involvement Stage IV Distant metastases including the liver <a href="#2_0">Go Back </a><ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 8 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) Clinical Features of Pediatric Ovarian Tumors: Median Age Features A – 5 Tumor <ul style="display: flex;"><li style="flex:1">Dysgerminoma </li><li style="flex:1">16 years </li><li style="flex:1">Rapid development </li></ul>Highly radiosensitive with excellent survival rates 14-25% with other germ cell elements  AFP, 75% Stage I high risk for relapse chemotherapy given to all patients Endodermal sinus tumor 18 years Teratoma <ul style="display: flex;"><li style="flex:1">Mature (solid, cystic) </li><li style="flex:1">10 -15 years Surgery mainstay of treatment </li></ul>Neuroglial implants may occur with solid or cystic types <ul style="display: flex;"><li style="flex:1">Immature </li><li style="flex:1">11 -14 years Amount of neuroepithelium determines grade </li></ul>Prognosis inversely related to stage and grade  AFP in 30% of cases <ul style="display: flex;"><li style="flex:1">Embryonal carcinoma </li><li style="flex:1">14 years </li><li style="flex:1">47% prepubertal; hCG and precocious puberty </li></ul>present; chemotherapy indicated Malignant mixed germ cell tumor <ul style="display: flex;"><li style="flex:1">16 years </li><li style="flex:1">40% pre-menarche; 30% sexually precocious </li></ul>AFP and hCG may be increased <ul style="display: flex;"><li style="flex:1">Gonadoblastoma </li><li style="flex:1">8 – 10 years Associated with dysgenetic gonads and sexual </li></ul>maldevelopment; treatment of choice – removal of both gonads Other (polyembryoma; choriocarcinoma) <ul style="display: flex;"><li style="flex:1">----- </li><li style="flex:1">Rare in children </li></ul>Castleberry, R. et.al. Germ Cell Tumors in Principles and Practice of Pediatric Oncology, Pizzo, P. and Poplack, D. (Eds). Lippincott-Raven Press Go Back <ul style="display: flex;"><li style="flex:1">A – 6 </li><li style="flex:1">Ovarian Mass – presence of a pelvic mass, right lower quadrant </li></ul>Resected Ovarian Mass - teratoma (Himesh Gupta, MD, St. Jude Children's Research Hospital) Go Back <ul style="display: flex;"><li style="flex:1">Module 13 - Document 17 </li><li style="flex:1">Page 9 of 12 </li></ul>Gonadal (Testicular and Ovarian Tumors) A – 7 International Federation of Gynecology and Obstetrics (FIGO) Staging for Ovarian Tumors <ul style="display: flex;"><li style="flex:1">Stage I: </li><li style="flex:1">Tumor limited to the Ovaries </li></ul>Stage IA: Stage IB: Stage IC: Limited to 1 ovary; no ascites. No tumor on external surface; capsule intact Limited to both ovaries; no ascites. No tumor on external surfaces; capsule intact Limited to one or both ovaries; tumor present on surface of one or both ovaries; or with capsule ruptured; or with positive ascites or positive peritoneal washings. <ul style="display: flex;"><li style="flex:1">Stage II: </li><li style="flex:1">Tumor involving one or both ovaries with pelvic extension </li></ul>Stage IIA: Stage IIB Stage IIC: Extension and/or metastases to uterus and/or tubes only. Extension to other pelvic tissues As in IIA or IIB with positive ascites or positive peritoneal washings; or with capsule ruptured. <ul style="display: flex;"><li style="flex:1">Stage III: </li><li style="flex:1">Tumor involving one or both ovaries with peritoneal implants outside </li></ul>the pelvis and/or positive retroperitoneal or inguinal lymph nodes; extension to small bowel or omentum; superficial liver metastases. Stage IIIA: Limited to true pelvis grossly with negative nodes but histologically confirmed microscopic seeding of abnormal peritoneal surfaces. Stage IIIB: Limited to one or both ovaries with negative nodes but histologically confirmed implants of abdominal peritoneal surfaces, none > 2 cm in diameter. <ul style="display: flex;"><li style="flex:1">Stage IIIC </li><li style="flex:1">Abdominal implants >2cm diameter and/or positive retroperitoneal or </li></ul>inguinal nodes. <ul style="display: flex;"><li style="flex:1">Stage IV: </li><li style="flex:1">Tumor of one or both ovaries with distant metastases outside the </li></ul>peritoneal cavity; parenchymal liver metastases; pleural effusion, if present, must have positive cytology.

Gonadal (Testicular and Ovarian Tumors)

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